title: Post-transcriptional regulation of human cathepsin L expression.
abstract: The expression of cathepsin L, a lysosomal protease, is known to be elevated in cancer and other pathologies. Multiple splice variants of human cathepsin L with variable 5'UTRs exist, which encode for the same protein. Previously we have observed that variant hCATL A (bearing the longest 5'UTR) was translated in vitro with significantly lower efficiency than variant hCATL AIII (bearing the shortest 5'UTR). Contrary to these findings, results of the present study reveal that in cancer cells, hCATL A mRNA exhibits higher translatability in spite of having lower stability than AIII. This is the first report demonstrating a highly contrasting trend in translation efficiencies of hCATL variants in rabbit reticulocytes and live cells. Expression from chimeric mRNAs containing 5'UTRs of A or AIII upstream to luciferase reporter cDNA established the A UTR to be the sole determinant for this effect. Transient transfections of bicistronic plasmids and mRNAs confirmed the presence of a functional Internal Ribosome Entry Site in this UTR. Our data suggest that differential stability and translation initiation modes mediated by the 5'UTRs of human cathepsin L variants are involved in regulating its expression.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Shivani
authors.initials: S
authors.lastname: Mittal
authors.forename: Riyaz A
authors.initials: RA
authors.lastname: Mir
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chauhan
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D056668:Cathepsin L / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009690:Nucleic Acid Conformation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020121:5' Untranslated Regions; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D056668:Cathepsin L